Evgeniy Perlov

Structured group psychotherapy in adults with attention deficit hyperactivity disorder: results of an open multicentre study.

Attention deficit hyperactivity disorder (ADHD) is a serious mental disorder that often persists in adulthood. In a pilot study, a structured skills training group program for adult ADHD led to significant symptomatic improvements. The present study evaluated the programs effectiveness, feasibility, and patient acceptability in a multicenter setting. Seventy-two adult ADHD patients were assigned to 13 two-hour weekly sessions at 4 different therapy sites. The therapy was well tolerated and led to significant improvements of ADHD, depressive symptoms, and personal health status (p < 0.001). The factors treatment site and medication did not contribute to the overall improvement. Patients regarded the program topics “behavioral analyses,” “mindfulness,” and “emotion regulation” as the most helpful. In this multicenter study, the therapy program showed therapist-independent effects and seemed to be disorder-specific. This warrants the effort of organizing further controlled studies.

Amygdala hyperreactivity in restrictive anorexia nervosa

Functional imaging studies had often investigated heterogeneous samples of anorexia nervosa (AN) patients with varying paradigms and methodologies that had resulted in divergent results. The present study aimed to examine these issues by studying a well-defined sample of restrictive AN patients with a disorder-specific paradigm which had been used previously. Subjects showed increased blood oxygen level dependent responses of the cingulate, frontal, insular and parietal cortices. Group comparisons demonstrated increased activity of the right amygdala in the sample of restrictive AN patients. Our results are in support of other recently published functional imaging studies and point to a pivotal role of the right amygdala in AN. Signals of the midcingulum were reduced in comparison to healthy controls. The constellation of increased activity of the amygdala and decreased activity of the cingulate cortex likely represents parts of a negative feedback loop of emotional processing. Disgust ratings correlated with the amygdala signal negatively, which points to the complex role of this structure within eating disorders.

Disturbed cingulate glutamate metabolism in adults with high-functioning autism spectrum disorder: evidence in support of the excitatory/inhibitory imbalance hypothesis.

Over the last few years, awareness of autism spectrum disorder (ASD) in adults has increased. The precise etiology of ASD is still unresolved. Animal research, genetic and postmortem studies suggest that the glutamate (Glu) system has an important role, possibly related to a cybernetic imbalance between neuronal excitation and inhibition. To clarify the possible disruption of Glu metabolism in adults with high-functioning autism, we performed a magnetic resonance spectroscopy (MRS) study investigating the anterior cingulate cortex (ACC) and the cerebellum in adults with high-functioning ASD. Twenty-nine adult patients with high-functioning ASD and 29 carefully matched healthy volunteers underwent MRS scanning of the pregenual ACC and the left cerebellar hemisphere. Metabolic data were compared between groups and were correlated with psychometric measures of autistic features. We found a significant decrease in the cingulate N-acetyl-aspartate (NAA) and the combined Glu and glutamine (Glx) signals in adults with ASD, whereas we did not find other metabolic abnormalities in the ACC or the cerebellum. The Glx signal correlated significantly with psychometric measures of autism, particularly with communication deficits. Our data support the hypothesis that there is a link between disturbances of the cingulate NAA and Glx metabolism, and autism. The findings are discussed in the context of the hypothesis of excitatory/inhibitory imbalance in autism. Further research should clarify the specificity and dynamics of these findings regarding other neuropsychiatric disorders and other brain areas.

Spectroscopic findings in attention-deficit/hyperactivity disorder: Review and meta-analysis

Objectives. The last decade has seen an increasing interest in the method of magnet resonance spectroscopy (MRS) since this is the only research tool that allows a non-invasive in vivo assessment of neurochemical aspects of ADHD without employing ionising radiation. In this paper we review published MRS results with respect to childhood, adolescence and adult ADHD. Method. We searched the Medline (Pub Med) database using the key words ADHD, attention-deficit/hyperactivity disorder, magnet resonance spectroscopy, MRS and spectroscopy. Citations of identified articles were also searched for relevant studies. Meta-analyses were performed for the measured metabolites and regions of assessment. Results. Sixteen studies could be identified that used MRS to investigate the neurobiology of ADHD. Two regions could be identified as the focus of spectroscopic investigations – the frontal lobe including anterior cingulate cortex and parts of prefrontal cortex and the basal ganglia, mostly striatum, alongside the fronto-striato-thalamo-frontal circuits. As for metabolites, in the majority of studies the ratios to creatine and not absolute concentrations of metabolites were estimated. Choline compounds, N-acetyl-aspartate and glutamate/glutamine (to creatine ratios) could be identified as being altered in several studies in ADHD. The meta-analysis showed increased choline compounds in several researched regions. Discussion. MRS is a promising tool for the non-invasive in vivo assessment of the cerebral neurochemistry in ADHD. More regions of interest (ROI) like amygdala, hippocampus, thalamus and cerebellum should be assessed in future studies. Further methodological improvements of MRS are desirable in order to assess the absolute metabolite concentration of several ROIs at the same time. Such developments will open novel perspectives in spectroscopic investigations of ADHD.

Effects of Group Psychotherapy, Individual Counseling, Methylphenidate, and Placebo in the Treatment of Adult Attention-Deficit/Hyperactivity Disorder: A Randomized Clinical Trial

IMPORTANCE Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder with high prevalence in adulthood. There is a recognized need to assess the efficacy of psychotherapy in adult ADHD. OBJECTIVE To evaluate the efficacy of cognitive behavioral group psychotherapy (GPT) compared with individual clinical management (CM) and that of methylphenidate hydrochloride compared with placebo. DESIGN, SETTING, AND PARTICIPANTS Prospective, multicenter, randomized clinical trial of 18- to 58-year-old outpatients with ADHD from 7 German study centers. Patients were recruited between January 2007 and August 2010, treatment was finalized in August 2011, and final follow-up assessments occurred in March 2013. INTERVENTIONS Sessions of GPT and CM were held weekly for the first 12 weeks and monthly thereafter (9 months). Patients received either methylphenidate or placebo for 1 year. MAIN OUTCOMES AND MEASURES The primary outcome was the change in the ADHD Index of the Conners Adult ADHD Rating Scale from baseline to the end of the 3-month intensive treatment (blinded observer ratings). Secondary outcomes included ADHD ratings after 1 year, blinded observer ratings using the Clinical Global Impression Scale, and self-ratings of depression. RESULTS Among 1480 prescreened patients, 518 were assessed for eligibility, 433 were centrally randomized, and 419 were analyzed as randomized. After 3 months, the ADHD Index all-group baseline mean of 20.6 improved to adjusted means of 17.6 for GPT and 16.5 for CM, with no significant difference between groups. Methylphenidate (adjusted mean, 16.2) was superior to placebo (adjusted mean, 17.9) (difference, -1.7; 97.5% CI, -3.0 to -0.4; P = .003). After 1 year, treatment effects remained essentially stable. Descriptive analyses showed that methylphenidate was superior to placebo in patients assigned to GPT (difference, -1.7; 95% CI, -3.2 to -0.1; P = .04) or CM (difference, -1.7; 95% CI, -3.3 to -0.2; P = .03). Regarding depression, no significant differences were found. In contrast, GPT was superior to CM for all visits in the Clinical Global Impression global assessment of effectiveness. CONCLUSION AND RELEVANCE Highly structured group intervention did not outperform individual CM with regard to the primary outcome. Psychological interventions resulted in better outcomes during a 1-year period when combined with methylphenidate as compared with placebo. TRIAL REGISTRATION isrctn.org Identifier: ISRCTN54096201.

Clarifying the Role of the Rostral dmPFC/dACC in Fear/Anxiety: Learning, Appraisal or Expression?

Recent studies have begun to carve out a specific role for the rostral part of the dorsal medial prefrontal cortex (dmPFC) and adjacent dorsal anterior cingulate cortex (dACC) in fear/anxiety. Within a novel general framework of dorsal mPFC/ACC areas subserving the appraisal of threat and concomitant expression of fear responses and ventral mPFC/ACC areas subserving fear regulation, the rostral dmPFC/dACC has been proposed to specifically mediate the conscious, negative appraisal of threat situations including, as an extreme variant, catastrophizing. An alternative explanation that has not been conclusively ruled out yet is that the area is involved in fear learning. We tested two different fear expression paradigms in separate fMRI studies (study 1: instructed fear, study 2: testing of Pavlovian conditioned fear) with independent groups of healthy adult subjects. In both paradigms the absence of reinforcement precluded conditioning. We demonstrate significant BOLD activation of an identical rostral dmPFC/dACC area. In the Pavlovian paradigm (study 2), the area only activated robustly once prior conditioning had finished. Thus, our data argue against a role of the area in fear learning. We further replicate a repeated observation of a dissociation between peripheral-physiological fear responding and rostral dmPFC/dACC activation, strongly suggesting the area does not directly generate fear responses but rather contributes to appraisal processes. Although we succeeded in preventing extinction of conditioned responding in either paradigm, the data do not allow us to definitively exclude an involvement of the area in fear extinction learning. We discuss the broader implications of this finding for our understanding of mPFC/ACC function in fear and in negative emotion more generally.

Visual cortex abnormalities in adults with ADHD: a structural MRI study.

Abstract Objectives. Most structural imaging studies in ADHD have focused on prefronto-striatal circuits. However, findings remained inconsistent while recent reports point to the posterior parietal cortex as an additional target for research. Moreover, although adult ADHD clinically differs from the childhood presentation little is known about the structural correlates of ADHD in adults. The aim of this study was to clarify the involvement of prefronto-striatal and posterior parietal areas in adult ADHD. Methods. Voxel-based morphometry of high resolution MRI scans was applied to analyze volumetric brain differences between 31 adult patients with ADHD and 31 control subjects. Results. The volume of prefrontal, striatal and parietal gray matter was normal. ADHD patients displayed a significant reduction of gray matter volume bilaterally in the early visual cortex (P < 0.04). Conclusions. The unexpected finding of visual cortex abnormalities might be related to impairments in early-stage, ‘subexecutive” attentional mechanisms. The results support the notion that executive dysfunction may not be the dominant neurobiological characteristic of ADHD at least in adult patients. The visual cortex deserves more consideration as a potentially important site of dysfunction in adult and possibly childhood ADHD.

Grey matter deficit in long-term recovered anorexia nervosa patients.

OBJECTIVE Cerebral grey matter (GM) reduction has repeatedly been shown in anorexia nervosa (AN). Evidence concerning completeness of GM restitution in recovered patients is contradictory. METHODS Five long-term recovered patients with AN were compared to symptomatic subjects and healthy controls using voxel-based morphometry. Whole brain GM, white matter and cerebrospinal fluid fractions were studied. Additionally, voxels that had shown significant GM reductions in symptomatic patients were investigated. RESULTS Recovered subjects had been severely affected when symptomatic (mean body mass index: 12.1 kg/m²) and were in remission for a very long time period (>5 years). Whole brain tissue fractions did not differ from controls. Regional analysis showed persistent GM volume reduction, in particular of the precuneus. CONCLUSIONS This study further supports the assumption that GM volume restitution is incomplete in subjects, who had previously been severely affected by anorexia nervosa. The meaning of GM reduction in long-term recovered AN patients, that is, its pathophysiological relevance, however, remains unclear. Furthermore, the precise aetiology of GM reduction remains an open question.

Immunological findings in psychotic syndromes: a tertiary care hospital's CSF sample of 180 patients

Immunological mechanisms and therapy approaches in psychotic syndromes were recently supported by the discovery of autoantibody-associated limbic and non-limbic encephalitis. However, how clinical diagnostic procedures in psychiatry should be adapted to these new insights is still unclear. In this study, we analyzed the cerebrospinal fluid (CSF) and neuroimmunological alterations and their association with cerebral MRI (cMRI) and electroencephalographic (EEG) findings. From 2006 to 2013, we acquired 180 CSF samples from psychotic patients. Between 2006 and 2009, CSF examinations were only performed in cases in which organic brain disease was suspected. Since then, this procedure has been integrated into our routine diagnostic workup. CSF basic diagnostics were supplemented by measuring antineuronal antibodies against intracellular synaptic antigens, antibodies against intracellular onconeural antigens, antibodies against neuronal cell surface antigens and thyroid antibodies. In addition, cMRIs and EEGs were conducted. We found white cell counts elevated in 3.4% of the cases, albumin quotient elevated in 21.8%, and protein concentration elevated in 42.2%. Evidence of intrathecal immunoglobulin synthesis was found in 7.2% of the cases. Antibodies measured against neuronal cell surface antigens were positive in 3.2%. Reactivity on antibodies against intracellular onconeural antigens were detected in 3.5%. Serum thyroid antibodies were elevated in 24.7%. Abnormalities were found in 39.5% of cMRIs and in 34.3% of EEGs. The main finding of our study was the high prevalence of CSF and autoantibody abnormalities in 54.4% of psychotic patients. In combination with cMRIs and EEGs, 75.6% showed abnormal findings. Our results are discussed with regard to the concept of immunological encephalopathy. Future studies should analyze the efficacy of immunomodulatory therapies.

H1-MR-spectroscopy of cerebellum in adult attention deficit/hyperactivity disorder

INTRODUCTION Neurobiological research has implicated the cerebellum as one possible site of neurophysiological dysfunction in ADHD. Latest theoretical conceptualizations of the cerebellum as core site of the brain to model motor as well as cognitive behavior puts further weight to the assumption that it might play a key role in ADHD pathophysiology. METHODS 30 medication free adult ADHD patients and 30 group matched (gender, age and education) healthy controls were investigated using the method of chemical shift imaging (CSI) of the cerebellum. The vermis, left and right cerebellar hemispheres were processed separately. RESULTS We found significantly increased glutamate-glutamine (Glx) to creatine (Cre) ratios in the left cerebellar hemisphere. No other differences in measured metabolite concentrations were observed. DISCUSSION To our knowledge this is the first evidence for neurochemical alterations in cerebellar neurochemistry in adult ADHD. They relate well to recent hypotheses that the cerebellum might control mental activities by internal models.